[Neurophysiological mechanism of brightness scaling]. A model of statistical decisions was used to reveal the measure of neural activity according to impulse reactions. Effectiveness of two possible measures was compared: number of spikes in groups and instantaneous frequency. The former one provides greater probability of correct estimation of brightness at a lesser error probability. Neurophysiological scales of brightness were obtained in the form of dependences of index d' on the stimulus intensity. The dependences were the power those in all cases of analysis. The exponent depends on the stimulus size and alters like the exponent of psychological scale for quantitative estimations on alteration of the stimulus space. The same dependence of subjective estimation on intensity of the light stimulut is preserved for psychophysiological scales of grouping on scaling by 5-, 10- and 20-grade scale of a single set of illuminations. This shows that the brightness neurophysiological scale formed at the first stage of perception is independent of the rules of decision making at the second stage of perception.


[Spontaneous activity of myenteric plexus neurons in the intact rabbit small intestine]. In rabbits intact myenteric plexus segments of the intestine, two types of neurons in regard to their electric discharges, were found: 1) units with single spontaneous spikes at the mean firing rate 2.3/sec and with interspike intervals from 140 to 900 msec; 2) units firing bursts of 3--12 spikes with interspike intervals of about 30 msec.


[Role of the intramural system of the cat colon in the organization of its rhythmic contractile activity]. Rhythmic contractility of the circular and longitudinal muscular layers of the cat colon in situ, after administration of blocking agents (atropin, phentolamine, and inderal), changes both in it spectral-frequency component and in the contraction strength of each layer, while the correlation between both layers contractions decreased from 69 to 28.9 percent. The colon rhythmic contractility is concluded to be a functionally organized process in conditions of intact innervation, the nervous system playing an active role in coordination of contractions of the circular and longitudinal muscular layers.


[Renal inhibitor of erythropoietin].

[Renal inhibitor of erythropoietin]. The soluble fraction of the rat and rabbit renal homogenate (normal, after acute blood loss or cobalt chlorate administration) contains an erythropoietin inhibitor and interferes with transformation of the renal erythropoiesis--stimulating factor into erythropoietin. After subcutaneous administration of this fraction in intact rats, an erythropoiesis inhibitor was revealed in their plasma.


[Heart energetics and adaptation of the organism to temperature]. In working isolated preparations of the rat heart, effects of prolonged adaptation of the organism to cold (1-3 degrees) or warmth (25-27 degrees) as well as 10-minus 6 M noradrenaline administration on the efficiency (E) of the heart mechanical work, were studied. In the cold adaptation E decreases, i.e. the amount of warmth released by the heart through the same amount of work, increases. In the warmth adaptation the heart E increases. The respective changes of the heart warmth production are only revealed in the working heart, as the temperature adaptation has no effect on the O2 consumption by the stopped heart. Contrary to the skeletal muscles, the heart E during the cold adaptation does not decrease under effect of noradrenaline. In the control and, particularly, during the warmth adaptation, the heart E decreases under effect of noradrenaline.


[Mechanism of development of training bradycardia]. Training bradycardia in rats and mice occurs in the result of an increase in the sensibility of the myocardium to acetylcholine, and a decrease of its sensibility to noradrenaline.


[Gastrin, cholecystokinin-pancreozymin, secretin and the interaction of the motor function of the stomach, duodenum and bile-secreting apparatus]. In chronic experiments on dogs, the motor function and electric activity of the smooth muscles of the stomach, duodenum, and gall-bladder were electrophysiologically and roentgenologically studied.


[Enzyme activity of the rat small intestine mucosa in conditions of repeated exposure to high ambient temperatures]. Acute experiments showed that daily 12-hr heating leads to different changes in fermentative activity (amylase, invertase, glycin-1-leycin-dipeptidase, monoglyceridiypase) in mucous membrane of the small intestine in white rats. These changes are due to not only the decrease of food consumption, but evidently are the result of functional changes in different organs and systems.


Comparison of the value of the two- and one-hour glucose levels of the oral GTT in the diagnosis of diabetes in Pima Indians. In many population and screening studies of diabetes, the one-hour glucose level of the GTT has been used to define the diabetic status of subjects. The one-hour postglucose load determination has been preferred over the two-hour value by many investigators primarily because of convenience and justified on the basis of the high correlation between the two values. Venous plasma glucose levels, one and two hours after 75-gm. carbohydrate load, were determined on over 1600 Pima Indians. In most sex and age groups, the frequency distributions of both the one-hour and two-hour glucose levels were clearly bimodal. By the logarithms of the glucose values these distributions were consistent with a model of two overlapping Gaussian distributions. The data indicate that for the Pima the amount of overlap of the distributions was greater for the one-hour than for the two-hour values. For each sex and decade the probabilities of misclassification of a normal as "hyperglycemic" and vice versa were smaller for the two-hour than for the one-hour values. Such misclassifications for the two-hour levels averaged 6.6 per cent and 11.6 per cent for the one-hour levels. The reproducivility of the GTT taken one to three weeks apart in a sample of ninety-nine Pima Indians showed that the two-hour level was superior to the one-hour level as measured by the mean values of the absolute difference between log GTT levels for test and retest values. The one-hour measurements also gave more disagreements between the classifications of diabetic status than the two-hour test values. If a single measure of glucose tolerance is to be selected for the diagnosis of diabetes among Pima Indians, these data provide a mathematical rationale for preferring the two-hour level to the one-hour determination.


Juvenile diabetes mellitus after forty years. Seventy-three patients with juvenile diabetes mellitus for a mean duration of 42.9 years were retrospectively studied on a multidisciplinary basis. Only three of this group of patients were socially disabled as a result of their long-standing illness. Of all the complications, insulin-induced hypoglycemia was most common. Although diabetic retinopathy was clinically evident in about 75 per cent of patients, only 50 per cent of these seventy-three patients had a significant visual impairment. Nephropathy was apparent in 59 per cent of patients, and neuropathy was demonstrable in half of them. Significant peripheral vascular system impairment was present in 40 per cent and major cardiac complication in 20 percent.


Gluconeogenesis from alanine in normal postabsorptive man. Intrahepatic stimulatory effect of glucagon. Although the stimulatory effect of glucagon on gluconeogenesis has been well demonstrated in certain systems in vitro, this effect has never been established in man. The present study was undertaken, therefore, to determine whether glucagon could stimulate gluconeogenesis from alanine in normal fasting man. Glucagon might stimulate this process by increasing the hepatic alanine uptake and/or by shunting the extracted alanine within the liver into the gluconeogenic pathway. In order to be able to examine these two aspects of gluconeogenesis, we combined the hepatic vein-brachial artery catheterization technic with an istopic infusion of alanine-14C. Alanine-14C specific activity was measured in whole blood and plasma by use of a rapid chromatographic technic. Since plasma contributed 93 per cent of the alanine extracted by the splanchnic bed with a specific activity three times that of the red blood cells, plasma alanine specific activity was used to study the conversion of alanine to glucose. A constant infusion of alanine-14C achieved a relatively stable arterial specific activity by forty minutes. The administration of glucagon by constant infusion (15-50 ng./kg./min.) had no affect on thf splanchnic extraction of alanine. Net splanchnic glucose-14C production, however, doubled during the glucagon infusion, and the conversion of alanine to glucose increased from 30 plus or minus 2 to 58 plus or minus 9 mumol/min. These data (1) demonstrate that in normal man fasted twelve to fourteen hours, glucagon at supraphysiologic levels can double the rate of gluconeogenesis from alanine and (2) indicate that this stimulatory effect of glucagon is exerted within the liver by shunting the extracted alanine toward new glucose formation rather than by increasing the hepatic extraction of alanine.


Agreement and discrepancy in the evaluation of normal and diabetic oral glucose tolerance test. Systematic analysis with a five-hour OGTT of 340 subjects representative of people likely to be examined in a center specialized in diabetes detection was performed by multiple discriminant analysis, which provides indices of discrimination for different sets of blood glucose (BG) values. The relative sensitivity and the relative specificity of six different diagnostic methods: Fajans and Conn, Wikerson, WHO, British Diabetic Association, UGDP, and European Study Group of Diabetes Epidemiology were computed, giving a quantitative determination for the degree of discrepancy in the definition of diabetes: only 48 per cent of the subjects are classified in the same way by any of the diagnostic criteria. The time(s) of sampling and the index or indices of OGTT which are the most efficient in screening diabetes were estimated from homogeneous groups of subjects universally recognized as nondiabetic (URND) or as diabetic (URD) according to the different diagnostic methods. Better discriminating power (DP) between URD and URND compared with the maximum DP as measured by D2 of Mahalanobis from the seven BG values of the OGTT is given by the two-hour (70.2 per cent) than by the one-hour (49.5 per cent) BG value when a single value is used; the one-two-hour BG value is the best set of two times (80.7 per cent). The different indices now in use for the classification of the OGTT have been found less effective than the weighted sum of one-two-hour BG values. The difficulty in obtaining highly specific diagnostic tests is discussed in relation to the consequences on a partly automated screening in large populations.


The relationship between diagnostic information obtained from three tests for detecting mild diabetes mellitus. The purpose of the study was to evaluate and compare the most commonly used criteria for the interpretation of the oral (OGTT) and intravenous (IVGTT) glucose tolerance tests and the intravenous tolbutamide test (IVTT) and to establish the criteria that give the highest degree of diagnostic agreement. The highest degree of diagnostic agreement was obtained with the following limits: a) blood glucose greater than or smaller than or equal to 120 mg/100 ml within 2 1/2 h after a 100 g OGTT together with b) a k-value of greater than or smaller than or equal to  1.05 as a limit for a 25 g IVGTT and c) a 30 min blood glucose level as percentage of fasting of greater than or smaller than or equal to 77 as limit for a 1 g IVTT. Using these criteria the three tests deemed the same subjects either diabetic or nondiabetic in about 2/3 of the cases. The best correlation between the blood glucose values of the OGTT and the k-values of the IVGTT and the 30 min values of the IVTT was obtained using the blood glucose concentrations of the last part of the OGTT. The 2 and the 3 hr values were however equal to the 2 1/2 hr values with regard to the degree of correlation with the values of the intravenous test. The results indicated that the diagnostic disagreement reported previously between the three tests may partly be due to the use of blood glucose values in the first part of the OGTT for the classification of the test and partly due to the screening limits chosen for interpretation of the three test.


The retinal blood flow in diabetes.

The retinal blood flow in diabetes. Retinal blood flow was studied in 9 normal volunteers and 36 diabetic patients. The method used was based on the measurement of the mean transit time of flourescein in the superior temporal quandrant of the retina and on estimation of the vascular volume by measuring vessels diameters. The results showed that patients with mild or no retinopathy had significantly increased volume flow compared with normals, those with moderate retinopathy had a slight but not significant increase and those with severe retinopathy had blood flow similar to that found in normals. The mean transit time was reduced significantly in those with mild or no retinopathy, but was similar to normals in those with moderate and severe retinopathy. Following succesful pituitary ablation and photocoagulation retinal blood flow was reduced compared with pre-treatment studies.


Relationship between changes of serum cholecystokinin-pancreozymin and serum insulin after different stimuli. The relationship between changes of serum immuno-reactive cholecystokinin-pancreozymin (CCK-PZ) and serum immuno-reactive insulin has been studied after various stimuli. The oral administration of 5 percent glucose or magnesium sulphate and the intra-duodenal administration of olive oil were all followed by a rise of serum CCK-PZ. The serum insulin rose after 5 percent glucose and also showed a small but insignificant rise with olive oil. There was, however, no change of serum insulin after the ingestion of magnesium sulphate suggesting that CCK-PZ in isolation does not stimulate insulin release.


Effect of ethynodiol diacetate and combination--type oral contraceptive compounds on carbohydrate metabolism. I. Six month intravenous glucose tolerance study. In order to evaluate long-term effects of different types of oral contraceptive compounds, blood glucose and plasma insulin levels were measured during an intravenous glucose tolerance test in 2 groups of normal, nondiabetic patients: 36 women using a progesterone-alone oral contraceptive, ethynodiol diacetate, and 36 women using a combination-type drug, containing norethynodrel and mestranol. Each patient was tested before and after 6 months of treatment. There were no significant differences from pre-treatment glucose and insulin values in the first group of women (on ethynodiol diacetate). In the second group (on norethynodrel and mestranol), there was a significant elevation of mean blood glucose levels at 15, 30 and 120 min of the glucose tolerance test. Nevertheless, a significant elevation of plasma insulin was seen only at 60 min of the test. Patients participating in this study will continue this treatment, and monitoring of carbohydrate metabolism is contemplated over a period of several years.


Thyroxine treatment and insulin secretion in the rat. Thyroxine treatment increases blood glucose and plasma insulin levels in the rat. The hypoglycemic effect of tolbutamide is more pronounced in treated animals. The immediate insulin secretory response of the isolated perfused pancreas to maximal, but not to submaximal, glucose stimuli was increased after thyroxine treatment, especially in the lower dose range. However, as thyroxine treatment reduces insulin release during the prolonged late phase, the total amount of insulin released from the pancreas is reduced. Both the early response to tolbutamide and the subsequent basal secretion were increased after thyroxine treatment. When the pancreas of treated rats was exposed to glucose plus pyruvate the inhibition of the late phase was reversed. Isoprenaline did not overcome the inhibitory effect of thyroxine treatment on the late phase of glucose-induced insulin release. Thyroxine induces a selective inhibition of glucose induced insulin release which is reversed by pyruvate; this indicates that thyroxine interferes with the glycolysis in the beta cell.


[Ovarian cancer in a monocygotic twin pair (Author's transl)]. We report on a female monocygotic twin pair, where the two women fell ill of an adenocarcinoma of the ovaries almost simultaneously. The paramesonephric epithelium of the coelom is discussed as origin for the disease. The concordance of the disease in the same environment points to the genetic factors is being more important in the development of the disease. Nevertheless a clearcut hereditary troit can not be defined at this time.


[Pregnancy in obese women (A'uthor's transl)]. Between 1969 and 1971 4,749 antenatal patients were observed. Compared to the tables for ideal weights of the Metropolitan Life Insurance Company Statistical Bureau, 26.76 percent of the patients were above ideal weight and 11.35 percent of the patients were obese. It was found that complications and illnesses during the pregnancy increased progressively with weight groups above the ideal weight. Hypertension was five times as frequent in obese women than normal, edema and proteinuria were common. Pre-eclampsia was more common in the obese. Varicosities occurred much more often in the maternity cases above normal weight and with obesity.


[Pregnancy in spite of multiple factors of infertility in both marital partners (Author's transl)]. Case report of two deliveries in a woman with an oligospermic husband who had a laparoscopic coagulation of the uterosacral ligament for endometriosis, followed by ulilateral salpingectomy and partial resection of the other tube for bilateral pyosalpinx. The tubal stump was stitched into the ovary. The case is reported to demonstrate that it is worthwhile to retain a minimun of chance for conception even in a case with a very bad prognosis.


[The timing of tubal ligation (Author's transl)]. In spite of medical or mixed medical and social indications, the sterilization by tubal ligation is frequently not carried out or done very late as in sterilization combined with a therapeutic abortion. This is borne out by the review of case histories and consultations of patients who had a sterilization operation other than post-partum, multiparous patients who had no sterilization, multiparous patients who had sterilization post-partum and patients who had an application for therapeutic abortion rejected and patients who had a therapeutic abortion with concomitant sterilization. The medical indications, medical social indications, the duration of the disease, the desire for child bearing, the social conditions and the family conditions were of such nature that in 29-80 percent of the cases under review sterilization could have been carried out at an earlier time. The relatively high incidence of women who presented with indications for sterilization but whose sterilization was delayed shows that more active individual counseling regarding sterilization by the attending physician is desirable. If necessary the physician should raise the question of sterilization and discuss the problem with the patient. This type of counseling would insure that the patient can make an informed decision and would minimize the psychological side effects and after-effects of sterilization.


[A rare indication for Caesarean section: the second twin. (Discussion of the paper by G. Scholtes: Geburtsh. u. Frauenheilk. 34 (1974) 448) (Author's transl)]. The discussion raises objections to this indication for Caesarean section. The indication for Caesarean section should become apparent prior to an attempt of vaginal delivery. A combined version of the second twin with intact membranes should eliminate some of the problems of internal podalic version with ruptured membranes. From 1971 to 1974, 43 twin deliveries (0.96 percent) occurred in 4,695 deliveries. There were two primary Caesarean sections. Four second twins were manually extracted. Five second twins were delivered by the Veit-Smellie Maneuver. One second twin was delivered by forceps and internal podalic version was used in 6 cases (13.9 percent). Three second twins died, one due to spontaneous antepartum umbilical cord complication, one due to fetal anomaly and one due to virus infection. The perinatal mortality for the second twin was therefore 6.9 percent. The author concedes that a combined version with intact membranes prior to an attempt of vaginal delivery may have been desirable in his cases but he reiterates that a Caesarean section for the second twin was the only way to obtain healthy live infants in his three exceptional cases.


[Influence of toxoplasma infection on the course of pregnancy and child development. Results of a prospective study]. This report gives a survey of the statistical evaluation in the combined study of "The course of gravidity and development of the child" in connection with toxoplasma infection which is sponsored by the German Research Council (DFG). In respect to the collected data it is possible to summarize as follows: 1. Neither the anamnestic nor the data of the observed gravidities allow the construction of a relationship between toxoplasma infection of a mother and the child after eliminating disturbing factors, especially that of the age (Tabelle 1-4 and Fig. 1). 2. An effect of prophylactic sulphonamide treatment in cases of latent and acute infected women has never been observed. The low number of abortions in the group of treated women is misleading because pregnant women with early abortion never received any treatment, therefore these people are included under the untreated group. 3. Up till now we have not observed a case of connatal toxoplasma infection in nearly 5,000 new born babies. After eliminating unreliable reports, abnormal developments which are thought to be related to toxoplasma infections have never been observed.


Age differences in learning, immediate and one week delayed recall. In an initial study, differences in learning and immediate recall were observed for groups of young and aged subjects on several measures. Retest date showed some differential loss for aged subjects after 1 week. Conclusions regarding long-term retention per se were not possible due to the nature of the design. In a second study, additional aged and young groups of subjects were run under delayed recall conditions. The data from these two groups were combined with data from the first study, with care taken to match subjects on a number of variables (health, education, intelligence). The results showed age-related differences for measures of learning and immediate recall but not for delayed 1 week retention.


Emotionality, exploratory behavior, and locomotion in aging inbred strains of mice. Two inbred strains of mice, C57BL/6J and DBA/2J, ranging in age from 2 to 38 months, were tested in an open field using the free exploration method. Scores were obtained for locomotor activity, exploratory behavior and emotionality. Strain differences were observed for all three variables. Beginning at late maturity (12 months), locomotor activity decreased with increasing age. Exploratory behavior was at a low level for DBA/2J mice at all ages. For C57BL/6J mice, exploratory behavior decreased significantly between 2 and 6 months and remained stable thereafter. Emotionality remained unchanged with advancing age for both strains of mice.


Testing the protein error theory of ageing: a reply to Baird, Samis, Massie and Zimmerman. A major prediction of Orgel's theory is that the misincorporation of amino acids into proteins will increase with age. This has not yet been tested experimentally. Indirect methods have been used to search for the presence of altered proteins in ageing cells or organisms, but these would not necessarily detect a low level of mistakes, nor do they distinquish between errors in synthesis and post-synthetic changes. Nevertheless, some experimental results have been obtained from genetic and biochemical studies with fungi and fibroblasts which confirm certain predictions of the protein error theory.


Biliary lipid output during three meals and an overnight fast. II. Effect of chenodeoxycholic acid treatment in gallstone subjects. Oral treatment with chenodeoxycholic acid causes dissolution of cholesterol gallstones in man. In order to determine the mechanism of this effect, we have measured 24-hour biliary lipid output, lipid composition of fasting gallbladder bile, and bile acid pool sizes before and during such treatment in six patients with radiolucent gallstones in functioning gallbladders. In all six patients, the degree of cholesterol saturation of fasting-state gallbladder bile was decreased during treatment to a level below the thermodynamic solubility line. This effect was due to a decrease in biliary cholesterol output, associated with conversion of more than 90% of the total bile acid pool to chenodeoxycholic acid. It could not be attributed to an increase in total bile acid pool size nor to an increase in biliary bile acid or phospholipid output.


A method to study cell proliferation kinetics in human gastric mucosa. The purpose of this investigation was to study cell proliferation kinetics in human gastric mucosa. Biopsies were taken from the antral and fundic part of the stomach through a fibre-gastroscope and incubated in culture medium containing a DNA-precursor (3-H-thymidine). Autoradiographs were prepared by the dipping technique. The number of labelled cells and the total number of cells in all cross sections of foveolae containing one or more labelled cells were counted. The labelling index (LI), which is defined as the percentage of labelled cells in the progenitor cell region, was estimated. When only cross sections with labelled cells are taken into consideration, the labelling index will be a little overestimated. In order to reduce this error a formula for correction was worked out. Thirty-six patients with different gastric diseases were studied. The observer error was minimal, and the results were highly reproducible. It was not possible to demonstrate any correlation between the labelling indices in antral and fundic mucosa. A significantly increased epithelial proliferation was found in fundic mucosa from patients with gastric cancer and atrophic gastritis.


Duodenogastric reflux: a cause of gastric mucosal hyperaemia and symptoms after operations for peptic ulceration. This study has investigated the possible association between duodenogastric reflux, gastritis, and symptoms in 35 patients with or without dyspepsia one to 15 years after gastric surgery. Five patients were excluded because of biliary disease, hiatus hernia, or recurrent ulceration. The remaining 30 were assessed by a symptomatic score, measurement, of bilirubin and sodium concentrations in samples of fasting gastric juice, endoscopy, gastric biopsy, and the presence of radiological reflux. In 15 patients with a symptom score of less than the median, gastric bilirubin levels were less than 1 mg/100 ml in 80%; severe endoscopic changes were seen in only one patient and reflux was not observed. In contrast, in patients with a symptom score in excess of the median fluoroscopic and biochemical reflux was seen in 69 and 80% respectively and severe mucosal hyperaemia in half. There was a significant correlation between symptoms, gastric hyperaemia, and duodenal reflus ( P smaller than 0-02).


Effect of metiamide on the response to secretin and cholecystokinin in man. The effects of intravenous metiamide on the pancreatic exocrine response to intravenous infusion of secretin plus cholecystokinin has been studied in eight patients with duodenal ulceration. The secretion of bicarbonate and water was not altered by metiamide. The secretion of enzymes was significantly less than control during infusion of metiamide. The differences between the pancreatic and gastric responses to metiamide are discussed.


Colonic and small intestinal response to intravenous prostaglandin F2 alpha and E2 in man. The effects of intravenous infusions of prostaglandins (PGs) F2 alpha(0-4 or 0-8 mug kg-1 min-1) or E2 (0-08 or 0-1 mug kg-1 min equals1) on net colonic movement of water and electrolytes and on ileal flow were measured in eight healthy males by simultaneous ileal and colonic perfusion. Ileal flow was increased by PGF2 alpha (six subjects) from a mean of 1-69 ml min-1 to 4-63 ml min-1 (P smaller than 0-01); it also increased in the two subjects given PGE2. Colonic absorptive function was not significantly diminished by either prostaglandin. These results suggest that diarrhoea due to prostaglandins originates in the small intestine.


The effect of intravenous prostaglandin F2 alpha and E2 on the motility of the sigmoid colon. The effect of a 20-min intravenous infusion of prostaglandin E2 (0-08 mug kg-1 min-1) or of prostaglandin F2 alpha (0-8 mug kg-1 min-1) on the segmental pressures in the sigmoid colon was studied in 12 patients. Prostaglandin F2 alpha had no measurable effect, but prostaglandin E2 significantly inhibited sigmoid motility.


Small bowel extracts in the inhibition of tumour growth. Results presented in this paper confirm earlier experiments which showed that microsomal extract of small bowel, preincubated with tumour cells, resulted in complete inhibition of tumour growth. However, experiments in vitro have shown that this effect is due to direct cytotoxicity of the extract and that (a) it is not specific for the small bowel; (b) it is not specific for tumour cells; and (c) the activity is predominantly in the mitochondrial fraction.


Deoxycholate depresses small-intestinal enzyme activity. Feeding sodium deoxycholate orally to rats for four days caused depression of the activity of the small intestinal enzymes lactase, sucrase, maltase, alkaline phosphatase, and N-acetyl-beta-glucosaminidase. The first four are brush border enzymes, the last a lysosomal enzyme. Alkaline phosphatase activity recovered very rapidly and rebounded to above the normal level within 24 hours. The activity of the three disaccharidases returned to normal within seven days while no recovery was observed within 96 hours of the activity of the lysosomal enzyme, N-acetyl-beta-glucosaminidase, after removing the bile salt from the diet.


Posterior mediastinal venous masses in patients with portal hypertension. Of 304 consecutive splenic venograms performed for suspected portal hypertension, oesophageal collateral veins were filled in 145. In seven patients massively dilated paraoesophageal collaterals were visible on the plain chest radiograph as a retrocardiac posterior mediastinal mass. Erect and supine radiographs have been compared in four patients, and the Valsalva and Mueller manoeuvres performed in one patient. The size of the masses was unchanged by these procedures, which were therefore of no value in differential diagnosis. The mass was still present immediately after portocaval anastomosis in one patient, but in another is no longer seen on radiographs taken seven years postoperatively. All seven patients also had submucosal oesophageal varices and therefore the barium swallow remains the most useful study to clarify the nature of a retrocardiac mass. Correct identification of pseudotumoural venous collaterals may avoid unnecessary further investigation.


Epidemiological aspects of Crohn's disease in Clydesdale 1961-1970. A retrospective study of Crohn's disease has been carried out in Clydesdale covering the decade 1961-1970. Three hundred and fifty-seven patients had acceptable evidence of either acute ileitis or of chronic granulomatous bowel disease. Of those fulfilling the criteria for inclusion in the study of chronic disease, 95% had accurate pathological and/or operative documentation of the lesions. Overall, females outnumbered males by 1-6:1 but colonic disease alone tended to affect females, particularly those over the age of 50. The annual incidence of all forms of the chronic disease in both sexes has increased during the decade, but diagnosis of colonic disease alone increased two-fold in the latter half of the study.


The vagus, the duodenal brake, and gastric emptying. It has been suggested that an intact vagal supply is essential for the normal function of the recptors in the duodenum and proximal small bowel, which influence the rate of gastric emptying. This paper reports the effect of vagal denervation on gastric emptying and also examines the site and mode of action of receptors in the proximal small bowel. It has been demonstrated in the dog that most, if not all, the receptors controlling gastric emptying lie in the proximal 50 cm of the small bowel. Following truncal vagotomy the emptying time of each instillation increased significantly and the differential rate of emptying of different instillations remained unchanged. The proximal 50 cm of small bowel was capable to differentiating between different instillates even after selective extragastric vagotomy, in which the duodenum was vagally denervated and, therefore, duodenal braking receptors function independently of vagal innervation.


The predictive accuracy of the postvagotomy insulin test: A new interpretation. Insulin-stimulated gastric secretion alone, without reference to basal secretion, has been examined in 45 male patients with duodenal ulcer in whom no gastric operation had been performed and in 124 patients following vagotomy for duodenal ulcer. Gastric juice was examined in terms not only of conventional indices, observed volume, titratable acidity and acid output, but also Vg, the volume corrected for pyloric loss and duodenal reflux. The range of secretion of the unoperated subjects was established in terms of peak and half-totwo-hour values for all indices. By reference to these ranges, secretion of postvagotomy subjects could be divided into two groups: (a) those with secretion within the preperative range, and (b) those with secretion less than the lower limit of the preoperative range. The best discrimination was given by Vg; those within the preoperative range (peak Vg in excess of 140 ml/hour and Vg half to two hours in excess of 105 ml/hour) had a 50% liability to recurrent ulcer, while those below the preoperative range had a zero liability to recurrent ulcer. Of the conventional indices acid output gave the best discrimination, which was almost as good as Vg. Peak acid output of 8 mmol/hour or acid output one half to two hours of 525 mmol/hour discriminated into two groups, with a 50% or zero liability to recurrent ulcer. Titratable acidity (Hollander's index of secretion), being highly susceptible to reflux, was not an adequate discriminant.


Stability of insulin-induced gastric secretion after vagotomy. Gastric secretory response to insulin-induced hypoglycaemia was stuided in 21 subjects following vagotomy and a drainage procedure for  duodenal ulcer. Eighteen subjects had one  early test, ie, within one  month of operation, and at least one late test, ie, six months or more after operation. Seven subjects had at least two late tests. When the insulin test results were expressed in terms of their Hollander status,there was as much variability with time as expected from previous reports. However, when results were expressed in terms of new criteria, decribed in the previous paper, the insulin status of postvagotomy patients remained constant with time.


Relative abundance of big and little gastrins in the tumours and blood of patients with the Zollinger Ellison syndrome. The relative concentrations of big gastrin (G-34) and little gastrin (G-17) were compared in the sera and tumours (gastrinomas) of Zollinger-Ellison syndrome patients. Big and little gastrins were identified in all 10 serum samples and in all 10 tumour biopsies examined. In serum, G-34 (range of concentrations 58-220 000 fmol/ml) was the major form of gastrin and G-17 (22-78 000 fmol/ml) was a minor component; the mean relative abundance of G-17/[G17 + G34]) in serum was 0-18 and the mean relative abundance of G-34 was 0-82. In tumour, however, the opposite was true: G-17 (49-869 000 pmol/g) was the major component and G-34 (45-464 pmol/g) a minor component, and the relative proportions of G-17 and G-34 were 0-73 and 0-27 respectively. Following an intravenous injection of porcine secretin (2-0 U/kg) there was a rapid increase in concentration of all forms of gastrin in the blood, but the increase in G-17 was proportionately greater than that of G-34 (relative abundance of G-17 in basal serum was 0-21 compared with 0-37, five minutes after secretin). Differences in the half lives of G-17 and G-34 may partly explain their relative abundancies in serum and tumour tissue.


The value of radiology in predicting gallstone type when selecting patients for medical treatment. Since medical treatment of gallstones is confined to cholesterol-rich stones, the ability of clinical radiographs to predict gallstone type was tested prospectively by comparing the preoperative radiological appearance of gallstones from 57 unselected patients with cholelithiasis coming to cholecystectomy with the subsequent analysis of the stones both by X-ray diffraction and by chemical techniques. Fifty-two per cent of the patients had 'non-functioning' gallbladders which failed to opacify after at least two contrast examinations and 25 out of 50 had radioopaque stones. Of the 25 patients with radiolucent stones, the stones in 20 ((80%) were predominantly cholesterol in type but radiology was misleading in five; three contained 40-55% calcium salts but were still radiolucent while two were amorphous and contained less than 10% cholesterol by weight on chemical analysis. While radiology was sometimes misleading when the stones were small and irregular, large radiolucent stones with a smooth profile were invariably cholesterol-rich stones. The results also show that in men calcified stones were commoner than in women and that in older women the gallstones contained more calcium salts and less cholesterol than in younger women less than 50 yr). This paper analyses critically the value and limitations of clinical radiology in predicting gallstone type.


Differential measurement of small and large bowel transit times in constipation and diarrhoea: A new approach. Differential measurements of small and large bowel transit times were performed in 13 subjects iwth a radiotelemetering pressure-sensitive capsule incorporating less than 10mugCi of 51-Cr. Six patients had constipation. The other seven patients had diarrhoea due to the irritable bowel syndrome (3), following vagotomy and pyloroplasty (3), or due to laxative abuse (1). This new method enables the gastric, small intestinal, and colonic transit times to be measured differentially in the same subject. The capsule can be localized in the gut lumen by reference to the characteristic pressure pattern and in relation to bony landmarks by the radioactive marker as frequently as desired without recourse to radiographs. The results show that gastric emptying and small intestinal transit did not differ in constipation and diarrhoea. By contrast the mean colonic transit was significantly faster (P smaller than 0.01) in diarrhoea whatever the cause (17.5 plus or minus 4.1 hours) than in constipation (118 plus or minus 4.1 hours).


Study of a yeast mutant with modified mitochondrial translocation of adenine nucleotides. I. Characterization of the op-1 mutant during mutagenesis with ethidium bromide. The effect of ethidium bromide on the growth of a yeast mutant with an impaired mitochrondrial translocation system of adenine nucleotides (op-1 mutant) was investigated. It was found that the op-1 mutant stops growing both under growing and non-growing conditions after treatment with ethidium bromide and that the growth cannot be restored by adding low-molecular compounds to the growth medium. It was the aim of the experiments to clarify whether the cessation of growth of the op-1 mutant after induction of the rho- mutation can be simulated by inhibitors phenotypically changing the mitochondrial function. It appears likely that the op-1 mutant stops growing only after the rho- mutation has been induced, because the phenotypic simulation of the rho- mutation does not lead the cessation of growth of the op-1 mutant.


Long-term observations of siamang behaviour. Long-term observations are presented on the behaviour of the siamang ape, Symphalangus syndactylus, in the lowland forest of central Malaya. The data were collected during two dry and three fruiting seasons between 1969 and 1973 inclusive on two groups with adjacent ranges; comparisons are made within and between sample periods, and between groups. The influence of weather on daily activities is considered. Food intake is analysed in terms of number of food trees, number of visits to these trees, and the cumulative time spent feeding on various food categories. Ranging behaviour is investigated in terms of distance travelled, area covered, and distribution of time and of food trees about the range. The occurrence of calling is described and compared with that of the white-handed gibbon in the same area. A discussion ensues on each of these aspects of behaviour in turn. Emphasis is laid on the similarity of behaviour of the two groups at any one time, and on the degree of their response to the fluctuations of environment variables. Finally, the application to siamang of ranging concepts currently used in animal behaviour is considered briefly.


Histomorphology of cervical and uterine epithelia of crab-eating macaque, Macaca fasciularis. Cytological characteristics and pattern of distribution of different cell types in the epithelia of cervix and uterus of crab-eating macaque (Macaca fascicularis) in follicular and luteal phases of the menstrual cyclic and amenorrhea were studied. The cervix uteri and uterus exhibit remarkable structural differenes in the ciliated, secretory, and ciliated-secretory cells. Since the number of ciliated-sexretory cells in the uterus is higher than in the cervix. It is believed that they form an additional source for the secretion of uterine fluid during the menstrual cylce. Both ciliated and secretory cells undergo degeneration; extensive cytoplasmic vacuolation associated with pycnosis and disorganization of the nuclei encountered.


Healed fractures in Macaca mulatta: age, sex, and symmetry. Previous studies utilizing series of wild-shot primates have suggested that there is an association between locomotor behavior, aggression and patterning of healed fractures. In this study, observations taken upon a series of 126 rhesus macaques which represent a total sample of a naturally occurring social group from Cayo Santiago, are used to reexamine the conclusions drawn from previous studies. As a control, a series of randomly collected rhesus skeletons from the same colony is examined. Major differences in pathology incidences by age, sex and laterality is indicated between the two groups. Possible explanation for cross-specific variability in fracture patterning are also considered.


Where to draw the nonprimate-primate taxonomic boundary. The known Cretaceous and Paleocene primates, the Paromomyiformes, although lacking a fully developed postorbital bar, are nevertheless, both cladistically and phenetically, closest to the common ancestor of the living primates. Not only their undisputed phylogenetic ties but also their early experiments inthe arboreal milieu necessitate their balanced evolutionary classification within the order Primates.


The order of movement of yellow baboons (Papio cynocephalus). The spatial organization of progressing baboons is thought to serve a protective function considered important in their adaptation to a terrestrial existence. Progression positions of identified black infants, adult males, and other yellow baboons were determined from repeated samples of troop movements. Spatial positioning by demographic class was similar to that previously found for three troops of anubis baboons living in two different habitats. Such consistency across species and habitats seems unlikely unless it arises from a common genetic background or common ontogenetic stabilizing mechanism.


A small gibbon-like hominoid from the miocene of Uganda. A new palate from Napak IV in Uganda, dated at 19 million years or older, provides information about the facial morphology of a small Miocene hominoid from East Africa. The fossil resembles small extant gibbons in most features of facial and papatal morphology that are preserved, more so than does its European contemporary, Pliopithecus (Epipliopithecus) vindobonensis. The Ugandan hominoid is most closely related to the small Kenyan hominoids formerly placed in the genus Limnopithecus.


Somatometry of newborn Macaca nemestrina. Cranial and postcranial anthropometric data were taken on 18 male and 14 female newborn Macaca nemistrina monkeys and compared with data from the literature on other species of Macaca. The females of every species are somewhat smaller in all dimensions than the males at birth. However, they are more fully developed than males in relation to the amount of growth needed to achieve the adult form, and therefore undergo less postnatal growth than males.


Weight growth of colony-reared chimpanzees. Body weight data, collected routinely from the US Air Force chimpanzee colony at Holloman AFB, was used for a longitudinal analysis of growth. Data were fitted to a model based on human growth patterns, which is described and compared to other treatments applied to growth data. Results are compared to other observations of chimpanzee and of human growth.


Territory and monogamy among Kloss' gibbons (Hylobates klossii) in Siberut Island, Indonesia. Behavior of Kloss' gibbons was studied from July 1 to October 7, 1972 in Siberut Island, off the coast of western Sumatra, Indonesia. Reproductive groups are monogamous families with a mean family size of 3.4 individuals (n = 11 families). Such families occupy territories averaging 6.7 ha. Adults defend their territories only against members of the same sex. This intrasexual defense of territory maintains the monogamous mating system. Other social units were unmated resident females, unmated resident males, floating males, and a courting pair. Males establish territories before mating, perhaps with help from their parents. Males guard their families against predators. Females lead progression through the territory. Subadults remain peripheral to their families but other family members tend to remain within 10 m of one another.


Administrative considerations in developing a volunteer program. A volunteer program can become a solid, smooth-functioning part of a community mental health center or other agency if it is built around the needs of both the agency and the volunteers. The author discusses the need to develop realistic job descriptions, to screen the applicants carefully, and to provide continued training and supervision both individually and in groups. She emphasizes that staff resistance to a volunteer program can be overcome by involving staff members in the program and by making them aware of the high quality of work the volunteers do.


Project Anchor: a study of an unsuccessful volunteer program to help former patients. The authors conducted a controlled research investigation into the effectiveness of a volunteer program at three Veterans Administration hospitals. In the program, called Project Anchor, volunteers helped mental patients being released from the hospital become reintegrated into their home communities. A total of 78 volunteers and 89 patients participated in the program; another 82 patients served as a control group. The researchers compared the two patient groups using data obtained through questionnaires, interviews, and hospital records. Analysis of the data indicated that the program had little therapeutic effect for the patients involved. The authors believe that the results are a forceful argument against an uncritical investment of treatment funds and personnel in outpatient volunteer programs, and that they raise serious questions about the proper role of the volunteer.


Development and evaluation of a training program for volunteers working in day treatment. When staff members of a community mental health center's day treatment program for adults with emotional problems found there was not enough time for planning and meeting program goals, they considered using volunteers to help in the treatment process. The center staff worked with the local mental health association to plan the training and use of volunteers. Twenty-five volunteers were initially selected and trained. They evaluated the training through questionnaires immediately after training and after three and six months of service. Respondents felt the training prepared them to perform their duties and understand their roles as volunteers. Volunteers have worked in the program for two and a half years; currently 28 volunteers each work approximately three hours a week.


Teaching transcendental meditation in a psychiatric setting. For two and a half years the authors have taught Transcendental Meditation (TM) to psychiatric patients at the Institute of Living in Hartford, Connecticut. They have also presented programs to hospital staff to acquaint them with the technique and practice of TM. In this paper they describe briefly the instruction program given to patients at the institute and point out some of the benefits of regular practice of TM for psychiatric patients.


Automated evaluation of goal-attainment ratings. At the Fort Logan Mental Center in Denver, an automated system for evaluating treatment effectiveness is based on a goal-attainment approach. Patients, staff, and patients' relatives or friends specify treatment goals from a standardized list of 703 goal statements. They rate the importance of each goal at the time it is set, and later rate the degree of goal attainment. The authors describe uses of the system and emphasize its value in obtaining information during treatment that can help improve the treatment process.


Senescence and human chromosome changes. Chromosome counts and a search for structural abnormalities were performed in cultured leukocytes from 60 elderly subjects (ages 62-96) and 60 controls (ages 10-13). A total of 3900 cells were examined, 3600 in 3-day cultured and 300 in cultivations maintained for 2 days. Our results and those obtained by other investigators indicate clearly that there is an increase in the level of aneuploidy and of structural abnormalities in the blood of aged persons. There is an excess of missing C-group chromosomes in elderly females, but no consistent preferential loss was observed among the males. In contrast with two previous studies, we found a significant decrease of aneuploid cells in 3-day cultures, as compared to those cultivated for 2 days only.


First determination of the isozyme patterns of phosphoglycerate mutases (E.C.2.7.5.3) and phosphoglycerate kinases (E.C.2.7.2.3) in human tissues. We present in this paper the first report about identification of several fractions of phosphoglycerate mutase (PGlyM) activity using starch gel electrophoresis and two different buffer systems. A typical muscle form of PGlyM was detected. It is also shown that isozymes of phosphoglycerate kinase (PGK) can be separated through the buffer system used by Spencer et al; (1964) for the phosphogluco mutase.


Population genetics of human red cell phosphoclucomutase isozyme PGM3 (E.C.: 2.7.5.1). Gene frequencies in Southwestern Germany. The polymorphism of the human phosphoglucomutase isozyme PGM3 can be demonstrated in erythrocyte hemolysates by means of horizontal starch gel electrophoresis. Gene frequencies from southwestern Germany are given. The frequency of the allel PGM-23 was estimated to be 0.232.


Phenotypic distributions of red cell glutamate-pyruvate transaminase (E.C.2.6.1.2) isoenzymes in British and New York populations. 1444 persons of British nationality living in London, and 294 Caucasians, 258 Negroes, 310 Hispanic persons, and 151 Chinese persons living in New York were tested for glutamate-pyruvate transaminase phenotype. The Gpt1 frequency in the British population was found to be 0.5277, the Gpt2 frequency was 0.4716, and two GPT 3-2 persons were found. The Gpt1 frequencies in the New York population were: 0.4834 in Chinese; 0.5226 in Hispanic persons; 0.8101 in Negroes; and 0.5306 in Caucasians. Two Caucasians possessed the GPT 3-2 phenotype.


Ring chromosome 13 in a polymalformed anencephalic. In the 33rd week of pregnancy an amniocentesis was performed because of low estriol. X-ray indicated the presence of anencephaly and a premature delivery was induced. Necropsy, in addition to anencephaly, showed a wide variety of malformations. The fetal karyotype determined from cultured amniotic fluid cells revealed a ring chromosome 13.


Platelet function in C6-deficient rabbits. Aggregation and secretion induced by collagen and zymosan. Platelet aggregation and the selective release of 5-hydroxytryptamine (5HT) and adenine nucleotides were measured in platelet-rich plasma (PRP) and washed platelet suspensions from control and C6-deficient rabbits. Aggregation and release induced by collagen were similar in both groups of animals. Aggregation responses to zymosan in control PRP samples were biphasic, and only the second phase was associated with release. In C6-deficient PRP samples, zymosan-induced aggregation lacked the second phase and there was no release of 5HT or adenine nucleotides. Zymosan induced no aggregation in washed platelet suspensions unless cell-free plasma was also added. C6-deficient plasma supported only primary aggregation, but the addition of control plasma resulted in biphasic aggregation and release. Zymosan which had been pre-activated in control or C6-deficient cell-free plasma induced primary aggregation in washed platelet suspensions. To obtain secondary aggregation and release, the addition of control plasma to the platelet suspension was necessary.


Cells involved in the immune response. XXVIII. the cellular composition of the lymphoid organs in the normal outbred rabbit. Horse anti-rabbit spleen cell antiserum was obtained by the intravenous immunization of horses with rabbit spleen cells. The antisera obtained were analysed for their lymphocytotoxic activity with respect to the lymphoid cells of the different lymphoid organs prior to and following absorption with the different lymphoid cells. The results have been integrated with those obtained in previous investigations and an all-embracing concept of the interrelationship of the lymphoid cells in the different lymphoid organs in the rabbit has emerged. The distinction between the heretofore considered central lymphoid organs (bone marrow and thymus) and peripheral lymphoid organs (spleen, lymph node and appendix) has been blurred by the finding that, at least in the rabbit, appendix cells possess specific antigen markers and participate in cell-mediated immune reactions in vitro and the observation that the spleen also has a central lymphoid function in the generation of cells in vivo capable of carrying out a cell-mediated immune reaction in vitro. It is concluded that the distinction of central and peripheral lymphoid function may be an artificial one in that it may reflect a function of the particular organ in only one of the many different types of immune reactions and that it should not influence the investigator in the elucidation of the cellular mechanisms participating in the mediation of the different immune responses.


Immunogenicity of lipid-conjugated protein in the intestine. Acylation of human serum albumin increases its ability to stimulate antibody formation in rats. This can be shown not only when the antigen was given intramuscularly but also when administered by injection into the lumen of the gut. A tendency of the modified molecules to attach to cells and to aggregate, increased anti-complementary activity, and reduced drainage through the lymphatics, have been demonstrated. The relationship of these features to the increased immunogenicity is discussed.


Dog immunoglobulins. II. The antibacterial properties of dog IgA, IgM and IgG antibodies to Vibrio cholerae. Secretory IgA antibodies to Vibrio cholerae were purified from the parotid saliva and mammary secretions of locally and orally immunized dogs using gel filtration, ion-exchange chromatography and anti-immunoglobulin immuno-absorbents. IgM and IgG antibodies were isolated from serum by gel filtration and ion-exchange chromatography. IgA antibodies proved to have minimal, if any, activity in direct killing of bacteria in the presence of complement or in the promotion of phagocytosis. The minimal activity which IgA had in these assays could be accounted for by extremely small quantities of IgM antibody. The same IgA antibodies, mixed with the challenge innoculum of Vibrio cholerae and fed to infant mice, protected these mice as efficiently as IgG or IgM antibodies.


Primary prosthetic replacement in acute femoral neck fractures. This paper reports a retrospective study of acute femoral neck fractures in 123 patients treated by primary prosthetic replacement. The average age in our patient population was 80-5 years. A Christiansen trunnion-bearing hip prosthesis (Christiansen, 1969 and 1974) was used in all patients except one. The prosthesis was cemented to the femoral shaft. The postoperative mortality rate was low, and the mortality rate was 8-7 per cent. The patients were examined between 6 months and 3 1/2 years after operation. Excellent or good results according to Stinchfield's hip assessment system (Stinchfield et al., 1957) were obtained in 82 per cent of the patients. We suggest that primary prosthetic replacement in acute femoral neck fractures in elderly patients is a safe and valuable procedure. However, a definite conclusion concerning this therapy cannot be drawn before a prospective study comparing the results of internal fixation and primary prosthetic replacement is made.


Analysis of fractures treated in the Royal Victoria Hospital, Belfast, in 1972, with special reference to gunshot wounds and bomb blast injuries. The total number of patients admitted to the Fracture unit in the Royal Victoria Hospital in 1972 is recorded and classified according to cause. Fractures resulting from gunshot wounds and bomb injuries are examined more closely together with associated injuries and complications. These groups are compared briefly with the open fractures resulting from road traffic accidents. Treatment of fractures in gunshot wounds and bomb injuries is discussed. Reference is made to the mechanisms of injury by gunshot and explosions.


Mountain rescue transport.

Mountain rescue transport. Death on Scottish mountains during a thirteen-year period were reviewed. Only five of 175 fatalities occurred during the stretcher journey: 200 patients were carried down alive. This review produced little evidence of serious harm from mountain rescue transport.


The long-term effect on the tibiofemoral compartment of the knee joint of comminuted fractures of the patella. We have studied the long-term effect of comminuted fractures of the patella with particular reference to the development of degenerative changes in the tibiofemoral joint. Degenerative changes which could convincingly be ascribed to the original injury were found in only one case, but we stress that the numbers are small, and that carefull search sould be made at operation for damage to the femoral condyles.


Evidence for the local denaturation of collagen fibrils during the mechanical rupture of human tendons. The ends of ruptured human tendons have been examined by scanning electron microscopy. The collagen fibres taper markedly, often leading up to a coiled segment or a knot of collagen at the point of rupture. This tapering of the collagen fibres was shown to be typical of denatured collagen by its selective removal by trypsin digestion. This denaturation caused by mechanical rupture was shown to be localized at the point of rupture, the rest of the collagen fibre remaining in the native state. The possible significance of these observations to the healing of ruptured tendons is discussed.


The use of seat belts by motor car occupants involved in road traffic accidents. Two hundred and forty-four motor car occupants involved in road traffic accidents, who sustained injuries sufficiently severe to require admission to hospital, have been investigated in order to assess the value of seat belts. The results indicated that the use of seat belts significantly reduced the mortality and the number of severe, multiple and facial injuries.


Dislocation and fracture-dislocation of the pelvis. Dislocation and fracture-dislocation of the pelvis is a major injury; the force involved in its production may not only disrupt the pelvis but result in extensive associated injuries. Between 1960 and 1968, 43 patients with this injury were treated in the Accident Service of the Radcliffe Infirmary. Their case records and radiography have been analysed and 29 of the patients re-assessed at a follow-up examination.


Avulsion of the gall bladder in blunt abdominal trauma. Traumatic avulsion of the gall bladder, and its subsequent dislodgement into the pelvis has not previously been reported. The case described records severe damage to the biliary system without much damage to other viscera.


Fracture of the sella turcica.

Fracture of the sella turcica. A patient with a fracture of the sella turcica, visible on lateral X-ray films of the skull, is described. This fracture, although not diagnosed during life, was present in approximately 20 per cent of a series of consecutive autopsies on patients who died of head injury. The significance of this injury to the hypothalamopituitary axis is discussed and methods of investigation suggested.


'Soccer supporter's wrist'.

'Soccer supporter's wrist'. Hyperextension injury to the wrists occured in seven adolescents attending football matches in this country. Clinical details of these injuries are recorded and the mechanism of injury is discussed.


The Fisk splint--description and assembly. The Fisk splint, the usefulness and adaptability of which have stood the test of time is described. Assembly and maintenance are easy, and serious difficulties are seldom encountered. I recomment its more widespread use.


Transient blindness following minor head injuries. Transient bliandness following minor head injury is a rare, although well known, and totally reversible entity. As the condition may have legal implications, a 5-year follow-up study was carried out on 4 young patients. Repeated ophthalmological, neurological and psychiatric examination both early nd late after injury did not reveal any organic or psychiatric diseases which might predispose to this disorder. The case reports, including one recurrent case, a follow-up study and a discussion of the aetiology are presented.


Haemodynamic defect in patients with severe head injury. Haemodynamic studies were made in 34 patients with severe head injury. The changes of cardiac output were noteworthy and correlated well with the clinical course and the prognosis of the patients. Marked systemic hypotension at the moment of brain death was mainly caused by the decrease of cardiac output. At this moment, peripheral resistance fell only to normal limits from the raised level. In the patients who survived, the cardiac output increased in proportion to the respiratory insufficiency, that is, the increased A-aDO2 and Qs/Qt. The increase of oxygen consumption was also accompanied by an increased cardiac output, but in the patients with the severest head injury who died, the cardiac output remained low. It failed to respond to increased A-aDO2 and Qs/Qt, and oxygen consumption remained low.


Lactoperoxidase activity in human milk and in saliva of newborn infants. Human milk and saliva from newborn infants were analyzed for their content of lactoperoxidase and thiocyanate. The activity of lactoperoxidase in infant saliva was variable but generally higher than that found in calf saliva. In contrast, the activity in human colostrum was low ( approximately 5%) compared with that found in cow's milk. The enzyme was resistant to gastric juice. Thiocyanate was demonstrated in infant saliva in concentrations about one-third of that in adult saliva. The amounts of lactoperoxidase and thiocyanate in infant saliva are quite sufficient to inhibit bacterial growth in in vitro systems. The importance of this system in vivo has not yet been demonstrated. The availability of this system to both newborn calves and humans (in calves provided largely by colostrum and in human babies by saliva) might be indirect evidence of its importance.


Platelet kinetics in canine ehrlichiosis: evidence for increased platelet destruction as the cause of thrombocytopenia. A significant (P < 0.025) increase in the mean platelet diameter occurred in five Ehrlichia canis-infected dogs when platelet numbers decreased to 100,000/mul or less. Maximal incorporation of [(75)Se]selenomethionine into platelets of six uninfected dogs was 0.080 +/- 0.019% (mean +/- standard error) and occurred 5 to 6 days after dosage, whereas maximal incorporation was 0.036 +/- 0.004% within 2 to 3 days after dosage in seven chronically infected dogs that had thrombocytopenia. Analysis of the [(75)Se]selenomethionine curves yielded a platelet lifespan of 9 days in uninfected dogs versus 4 days in chronically infected dogs. Thus, megakaryocyte maturation and/or platelet release occurred at an accelerated rate in infected dogs, whereas increased destruction of newly produced labeled platelets diminished their number of peripheral blood. [(51)Cr]sodium chromate-labeled platelet survival was exponential, with a half-life of approximately 1 day in two dogs at 2 to 4 days postinfection and three chronically infected dogs. Platelet survival time was 8 days and rectilinear in four uninfected dogs. Platelet recovery was 39.43 +/- 2.86% in infected dogs as compared with 68.2 +/- 10.72% in uninfected dogs. Whole-body scans of one dog prior to and 7 days after infection showed that labeled platelets were destroyed primarily in the spleen. It is concluded that the thrombocytopenia in E. canis-infected dogs is the result of increased platelet destruction which begins within a few days after infection.


Association of Streptococcus mutants with human dental decay. The association of Streptococcus mutans with human dental decay was investigated by using several types of samples: (i) paraffin-stimulated saliva samples taken from children with from 0 to 15 decayed teeth; (ii) pooled occlusal and approximal plaque taken from children with no decayed or filled teeth, or from children with rampant caries of 10 or more teeth; (iii) plaque removed from single occlusal fissures that were either carious or noncarious. The results showed a significant association between plaque levels of S. mutans and caries. The strongest association, P < 0.0001, was found when plaque was removed from single occlusal fissures. Seventy-one percent of the carious fissures had S. mutans accounting for more than 10% of the viable flora, whereas 70% of the fissures that were caries free had no detectable S. mutans. Sixty-five percent of the pooled plaque samples from the children with rampant caries had S. mutans accounting for more than 10% of the viable flora, whereas 40% of the pooled samples from children that were caries free had no detectable S. mutans. Saliva samples tended to have low levels of S. mutans and were equivocal in demonstrating a relationship between S. mutans and caries.


Complement-dependent anaphylactic reactions. The concept of elicitation of reactions of anaphylactic type by non-tissue-fixing antibody, through activation of complement and release of anaphylatoxins by antigen-antibody complexes in vivo, is not clearly defined by published evidence. Experimental data are presented to demonstrate that guinea pig immunoglobulin G2 (noncytotropic) complexed with antigen in vitro elicits dermal reactions in guinea pigs, and that pretreatment of animals with complement-inactivating cobra venom factor diminishes such reactions. The various pathways through which immediate hypersensitive reactions may occur are discussed.


Differential effects of homocytotropic antibodies on the mast cell and anaphylactic responses in actively and passively sensitized mice. The relationship between mast cell degranulation, anaphylaxis, and the production of homocytotropic antibodies was examined in ICR mice after trichinella infection. It was found that the active cutaneous response to trichinella antigen had a rapid onset (within 2 weeks) and the sensitivity increased over a 9-week period after infection. Two types of mast cell degranulation were observed: (i) moderate, with few extracellular, deep-blue-staining granules (May-Grunwald-Giemsa), and (ii) "explosive," with many extracellular reddish-staining, swollen granules, indicating an apparent breakdown of cell membrane. The moderate type was observed primarily during the first 4 weeks after infection, whereas the explosive type predominated during 5 to 8 weeks. Homocytotropic antibody of the immunoglubulin G(1) type appears responsible for moderate type degranulation, and mouse immunoglobulin E appears responsible for the explosive degranulation. No correlation was evident between the active cutaneous anaphylactic response and either type of degranulation or between active cutaneous anaphylaxis and circulating levels of homocytotropic antibody. A proposed role of immunoglobulin G(1) and mouse immunoglobulin E in immunity is discussed.


Chromosomal synthesis of staphylococcal exfoliative toxin. Tox-+ staphylococcal strains, as opposed to Tox-minus strains, produce epidermal exfoliation within 18 h after direct subcutaneous or intraperitoneal injection into newborn mice. The extracellular product responsible for exfoliation is termed exfoliative toxin (ET). When culture supernatant fluid from the plasmid-cured Tox-minus  substrains UT 0100 or UT 0111 or from six naturally occurring phage group 2 Tox-minus strains was concentrated 20-fold and inoculated into newborn mice, ET activity could be detected. The Tox-minus, cured derivatives produced ET at levels which were 32 minus and 64-fold lower than the amounts made by their Tox-+ parent strains. Since these Tox-minus, cured substrains contained no plasmid deoxyribonucleic acid, it was postulated that the product possessing ET activity in strains UT 0100 and UT 0111 was made by chromosomal genes. This product has been isolated and purified from strain UT 0100 and appears as two faint bands after electrophoresis on polyacrylamide gels and corresponds in position to a heavy band of ET isolated from the Tox-+ strain UT 0007.


Effect of temperature on phagocytosis by human polymorphonuclear neutrophils. Monolayers of human peripheral blood polymorphonuclear neutrophils and 14C-labeled Staphylococcus aureus were incubated at various temperatures. The rate and extent of phagocytosis was unchanged between 33 and 41 C but was depressed above and below this range


Demonstration by immunoelectro-osmophoresis of precipitating antibodies to a purified rubella virus antigen. The nonionic detergent Triton X-100 was used to extract antigens of rubella virus from infected tissue culture cells. Three virus-specific antigens were demonstrated by crossed immunoelectrophoresis by using a pool of human gamma globulin as antiserum. The most dominant of these antigens were purified by ion-exchange chromatography on diethylaminoethyl-cellulose. This antigen was of glucoprotein nature and had slow electrophoretic motility and low binding capacity to diethylaminoethyl-cellulose. Thus, it seems likely that the antigen is identical with the precipitating antigen of rubella virus designated b-antigen or tro-osmophoresis with precipiting antibody in sera obtained from patients recovering from acute postnatal rubella. The precipitin reaction that could be correlated to the hemaglutination-inhibition titers of the same sera appeared 12 days after onset of the disease and remained positive for several years.


Virulence of Streptococcus mutans: a sensitive method for evaluating cariogenicity in young gnotobiotic rats. Gnotobiotic rats infected with Streptococcus mutans 6715 at 19 days of age and fed a purified diet (305) containing 5% sucrose developed extensive caries lesions on all molar surfaces within 16 days (35 days of age). Approximately twice as many lesions developed when infected rats were maintained until 45 days of age, whereas noninfected rats did not develop caries when fed diet 305. Gnotobiotic rats infected with S. mutans 6715 and fed a purified diet containing no sucrose (300) until day 25 and subsequently fed diet 305 for 10 days developed lesions similar to rats fed diet 305 for 16 days. Furthermore, rats infected with S. mutans 6715 and fed diet 300 until 45 days of age developed approximately one-half the smooth surface lesions as infected rats fed diet 305 for the same length of time. The level of caries on buccal and proximal molar surfaces in 45-day-old gnotobiotic rats varied when animals were infected with S. mutans AHT, BHT, NCTC 10449, 6715, or LM-7. Animals infected with S. mutans AHT showed more severe lesions on the buccal surfaces than those observed in animals infected with the other strains of S. mutans tested, whereas S. mutans 6715 caused significantly more caries on proximal surfaces. On the other hand, rats infected with S. mutans LM-7 exhibited the lowest level of caries on all molar surfaces of the five strains of S. mutans tested.


Extracellular enzymes of Micropolyspora faeni found in moldy hay. Fully active enzymes with chymotrypsic activity were demonstrated in moldy hay samples where Micropolyspora faeni was found as the predominant saprophyte by using polyacrylamide gel electrophoresis. Great quantitative differences in enzymatic activity were found among moldy hay samples.


Opsonizing antibodies, host factors, and the limulus assay for endotoxin. The role of endotoxin in the pathophysiology of human gram-negative rod bacteremia is controversial. Gelation of lysates prepared from the amebocytes of Limulus polyphemus is a highly sensitive means for quantifying endotoxin-like activity in vitro, but variable results have been reported in several clinical studies. We performed limulus tests on plasmas obtained simultaneously with culture-positive blood from 68 patients with gram-negative bacteremia and related results to heat-stable opsonizing activity against the autologous infection strain. Overall, limulus positivity was 52% in this series. Positive tests were observed with 78% of plasmas with opsonic titers is less than or greater to 1:20 but with only 27% of plasmas whose titers were is greater than or equal to 1:80 (P less than 0.005). There was a strong association of positive tests with leukopenia. thrombocytopenia, and more severe underlying disease. In vitro study showed a 10-fold reduction in the sensitivity of the gelation test by antibodies against the endotoxin used and an additional 10-fold reduction when the test system included phagocytic cells.


Chrysanthemum pollinosis in Japan.

Chrysanthemum pollinosis in Japan. Using the scratch test with self-made chrysanthemum pollen extract of 32,700 PNU/ml, a positive response was elicited in 60 of 316 patients (18.9%) with allergic rhinitis and bronchial asthma, and was positive in 42.5% adults with allergic rhinitis. On the other hand a 4.7% positive response was obtained in 84 non-allergic subjects. With the intracutaneous test, a threshold value was determined in 7 cases with 0.327 PNU/ml; 12 with 3.27 PNU/ml; 8 with 32.7 PNU/ml; and 8 with 327 PNU/ml, as opposed to one positive in 84 controls with 327 PNU/ml (1.3%). P-K tests were successfully done in 15 out of 16 cases. Furthermore, the results of in vitro neutralization tests using chrysanthemum and other compositae pollen extracts indicated the absence of sharing antigenic determinants between them. Provocation tests were conducted in 4 cases of allergic rhinitis and 3 cases of bronchial asthma with positive response in all the patients. From these results it was found that chrysanthemim pollinosis indeed exists in Japan, particularly in the mountainous districts.


Chorioallantoic membrane heterotransplantation of human brain tumors. Specimens of human tumors were taken from the operating room and directly heterotransplanted to chick chorioallantoic membranes. Seventy-one percent of the eggs survived the procedure and 41% of the tumors appeared viable after 1 week. Microscopically, the first-generation heterotransplants resembled the parent tumors. Many specimens showed evidence of growth, but in most of them there was also some degree of necrosis. The necrosis increased with serial heterotransplantation, so that tumor propagation usually was not possible beyond the second to third transplant generation; nevertheless, it was found that almost any histological type of intracranial tumor could be grown for short periods of time at least on the chick chorioallantoic membrane.


Regression of spontaneous mammary tumors in dogs after injection of neuraminidase-treated tumor cells. The effect on tumor progression produced by the injection of VCN-treated tumor cells in dogs with spontaneous mammary tumors was investigated. Untreated dogs of different races and different ages with at least two palpable spontaneous mammary tumors were selected. One of the tumors was left in the animal for further clinical examination whereas the other tumor(s) was (were) excised for preparation of a single-cell suspension by mechanical disintegration and enzymatic digestion with collagenase and trypsin. (1) In the first group, each animal was infected with 2 times 10-7 similarly prepared autologous, mitomycin-treated tumor cells; in 8 out of 12 dogs of this group the tumors progressed while so far 1 dog has died of metastasis. (2) In the second group, each animal received the same number of 2 times 10-7 tumor cells, which were mitomycin- and VCN-treated: 13 out of 15 dogs had a significant regression of their tumors to less than 10% of the original volume; in 1 dog the tumor remained unchanged and in 1 dog it progressed. (3) In the third group, 8 dogs received 1 times 10-8 mitomycin- and VCN-treated tumor cells: the application of this cell dose resulted in an accelerated tumor progression in all 8 dogs, 3 of which have already died of metastasis. The significance of these findings, with respect to potentiation and abrogation of the immunological response and with regard to immunotherapy in man, is discussed.


Studies on a gross-virus-induced lymphoma in the rat. II. The role of cell-membrane-associated and serum P30 antigen in the antibody and cell-mediated response. The internal viral protein, p30-1, has been identified by cytotoxicity tests using xenogeneic sera, on MuLV-G-induced rat lymphoma cells. In this system internal virion antigens, and in particular p30, are  cytotoxic target antigens for syngeneic antibody and cell-mediated cytotoxicity; p30 is also present in the serum of rats with progressively growing lymphomas, and is the principal antigen responsible for the inhibition of cell-mediated cytotoxicity produced by these sera.


Erythropoietin-independent erythroid colony formation in vitro by hemopoietic cells of mice infected with friend virus. We have investigated the production of erythroid colonies in plasma culture by bone-marrow and spleen cells taken form C3Hf/Bi mice previously infected with a polycythemic strain of Friend virus (FV). Inclusion of erythropoietin (Epo) in the medium was found unnecessary for erythroid colony formation in vitro by these cells, although it was essential for the production of erythroid colonies by hemopoietic cells from normal animals. Development of erythroid colonies also proceeded umimpeded when cells from FV-infected animals were cultivated in medium pretreated with rabbit anti-serum that was shown to inactivate Epo. Thus, the hemopoietic tissues of FV-infected mice contained erythroid colony-forming units (CFU-Es) which appeared to be Epo-independent. When spleen cells from FV-infected mice were exposed to antiserum directed against syngeneic FV-infected spleen cells and complement, and then cultured with or without Epo, the number of erythroid colonies that developed was drastically reduced, indicating that the CFU-Es in these animals carried FV-induced antigen(s), and must themselves have been infected with virus. Electron microscopy of erythroid colonies produced by cells from FV-infected mice revealed the presence of budding and abundant free type-C virus particles. The efficiency of erythroid colony formation in vitro either with or without Epo by hemopoietic cells from FV-infected mice was substantially increased over that of cells from normal mice. The increase in the number of CFU-Es in these animals was due mainly to an increase in the number of Epo-independent CFU-Es. Epo-independent CFU-Es were first detected in bone marrow and spleen as early as 3 days after FV infection; thereafter their numbers progressively increased for at least 9 days. Hypertransfusion with red blood cells prior to FV infection reduced, while bleeding greatly increased, the efficiency of erythoid colony formation without Epo by cells from the spleens of the infected mice. The phenomenon of erythroid colony formation in plasma cultures lacking Epo provides a sensitive and reliable means of detecting Epo-independent CFU-Es, which appear to play a fundamental part in pathogenesis of the disease resulting from infection with the polycythemic strain of FV.


Dietary vitamin A and human lung cancer. Five-year follow-up results for 8,278 men who in mail surveys had reported their cigarette smoking and dietary habits showed: (1) an index for vitamin A intake to be negatively associated with lung cancer incidence at all levels of cigarette smoking;(2) this association to be more clearly expressed in the subset of histologically proven pulmonary carcinomas other than adenocarcinoma; and (3) the positive association between cigarette smoking and lung cancer to obtain irrespective of the dietary level of vitamin A or related factors. The findings are in accordance with experimental results on animals and call for further exploration of the role of nutritional factors in the development of human lung cancer.


Environmental factors and cancer incidence and mortality in different countries, with special reference to dietary practices. Incidence rates for 27 cancers in 23 countries and mortality rates for 14 cancers in 32 countries have been correlated with a wide range of dietary and other variables. Dietary variables were strongly correlated with several types of cancer, particularly meat consumption with cancer of the colon and fat consumption with cancers of the breast and corpus uteri. The data suggest a possible role for dietary factors in modifying the development of cancer at a number of other sites. The usefulness and limitations of the method are discussed.


Anti-tumour antibodies in normal mouse sera. Evidence for the involvement of the immune system in surveillance against nascent tumors was sought by testing whether normal mouse sera were cytotoxic in the presence of rabbit complement for a variety of lymphoid and non-lymphoid tumor-cell lines. Tumour-reactive antibodies were detected in all mouse sera tested, including sera from congenitally athymic (nude) mice. Considerable variation was noted, however, in the levels of naturally occurring antibodies against specific tumor antibodies were identified as being predominantly IgM. The possible relevance of natural anti-tumor antibodies to immune surveilance was discussed.


The effect of non-ionic detergent tween 80 on colcemid-resistant transformed mouse cells in vitro. The effect of the non-ionic detergent tween 80 on one colcemid-resistant and one sensitive subline of mouse L cells has been studied. The colcemid-resistant subline was also resistant to colchicine and Vinca alkaloids. Tween 80 at concentrations of 0.01% (v/v) or higher increased the sensitivity of drug-resistant cells to the antimitotic effect of colcemid, colchicine and vinblastine. Tween 80 also potentiated the initial rate and the maximal level of the (3-H)-cholchicine uptake by both sensitive and resistant cells. However, the detergent at concentrations of up to 1% had no effect on (3-H)-colchicine binding by cell homogenates. Thus it appears that the effects of tween 80 were due to an increase in cell membrane permeability to the drugs. The effect was completely reversible. The cells did not become adapted to the sensitizing action of tween 80 even after prolonged incubation in medium containing the detergent. A considerable increase in the permeability to the drug was obtained with doses of tween 80 which were non-toxic and which had no effect on cell proliferation, morphology and locomotion. The increase in membrane permeability caused by tween 80 at these concentrations was selective, the membrane permeability to ions and to (3-H)-2-deowy-D-glucose being, in fact, unchanged.


The mechanism of carcinogenic action of 1,2-dimethylhydrazine (SDMH) in rats. The radioactivity level in blood, bile, urine and contents of parts of the gastro-intestinal tract in rats was studied after subcutaneous administration of 3-H-1,2-dimethylhydrazine (3-H-SDMH) which induces colonic tumours. The alkylation of DNA, RNA and protein in the intestinal mucosa, liver and kidneys was estimated 1 h to 28 days after 3-H-SDMH treatment from the 3-H-incorporation into these macromolecules. Administration of 3-H-1,2-diethylhydrazine (3-H-SDEH) which does not induce intestinal tumours was made as a control. Fifteen to 30 min after 3-H-SDMH treatment, marked radioactivity was found in blood, bile, urine and in contents of all regions of gastro-intestinal tract. After 3-H-SDMH administration no label occurred in the contents of localized segments of gastro-intestinal tract although it was present in blood, bile and urine. 3-H-SDMH methylated DNA, RNA and proteins of intestinal mucosa, liver and kidney to a high degree. One hour after 3-H-SDMH treatment the incorporation of label into protein of intestinal mucosa was higher than into liver and kidneys. 3-H-SDEH did not alkylate macromolecules in these organs but did so in thymus, spleen and brain, which are target organs for this carcinogen. After total hepatectomy, 3-H-SDMH did not methylate macromolecules of the intestinal mucosa. The following mechanism for the carcinogenic effect of SDMH is suggested. A carcinogenic metabolite of SDMH forms, in the liver, a conjugate with glucuronic acid. This glucuronide enters the gut both with bile and directly via the circulation. Microbial beta-glucuronidase releases the active metabolite which, in turn, alkylates tissue macromolecules.


Cancer of asians in kenya.

Cancer of asians in kenya. The frequency of various cancers among Indian immigrants in Kenya was compared to corresponding data among native Africans and Indians in the regions of India from which most of the studied population originally migrated. The Kenyan Indians do not have the cancer pattern of their home country nor do they have the cancer pattern of indigenous Africans. They have instead, like Europeans and North Americans, a higher risk of cancer of the lung, breast and the large intestine. It is suggested that this is related to enbironmental factors and variations in living habits.


Prostaglandin synthesis inhibition: effect on bone changes and sarcoma tumor induction in balb/c mice. An increase in prostaglandins (PGs) of the E series has been demonstrated in Moloney sarcoma virus (MSV)-induced leg tumors of 6-week-old BALB/c male mice. The level of the hormone has been shown to increase with the tumor diameter and decrease with tumor regression. At the peak of tumor size the tibial bones of the mice were considerably deformed, suggesting osteoclastic activity. The systemic calcium level was not elevated, indicating possible release of calcium into the local tumorous area. In mice treated with indomethacin the tumors failed to develop and PG levels were markedly lower. Tibial bones of treated mice were similar in appearance to those of control, non-tumorous mice. PG levels of DBA/1J mice bearing extensive Cloudaman S91 melanomas were not elevated and no bone deformation was seen. When contrasted with studies of immuno-depressed mice the results suggest that indomethacin acted in conjunction with and possibly to restore the PG-induced depression of the immune system in preventing tumor development. It is also hypothesized that indomethacin, by suppressing the PG-mediated calcium release from bone, could be operative in inhibiting tumor growth.


Establishment of a continuous tumor-cell line (panc-1) from a human carcinoma of the exocrine pancreas. An epithelioid cell line, started from a human pancreatic carcinoma of ductal cell origin, has been maintained in culture for over 2 years and has been subcultured more than 40 times. The PANC-1 cell line has a doubling time of 52 h and G6PD activity of the slow mobility of B type. Chromosome studies show a modal number of 63 with three distinct marker chromosomes and a small ring chromosome. The malignant nature of the PANC-1 cell line was verified by: (1) the ready growth of PANC-1 cells in soft agar and on top of a fibroblast monolayer; and (2) the formation of a progressively growing anaplastic carcinoma after injection of a nude-athymic mouse with PANC-1 cells.


Isolation and characterization of a homogeneous isomeric species of carcinoembryonic antigen: cea-s. A single homogeneous isomeric species of carcinoembryonic antigen was isolated by reference to solubility in 0.9 M perchloric acid, isoelectric focusing, molecular exclusion chromatography, ion exchange chromatography, passage through immuno-absorbants, and isopyknic density gradient ultracentrifugation. The final product, representing approximately 1.8% of the perchloric acid soluble glycoprotein of the tumor, is homogeneous and devoid of other proteins by polyacrylamide gel electrophoresis. This single species of carcinoembryonic antigen, CEA-S, has a sedimentation velocity of 6.6, a diffusion constant of 3.05 times 10-minus 7 cm-2/sec, a mean Stokes radius of 65 A, a density of 1.41 ml/g in cesium chloride and an estimated molecular weight of 181,000, and it is devoid of detectable A or B blood-group antigens. Immunochemical studies demonstrate qualitative similarities between CEA-S and conventional carcinoembryonic antigens; however, competitive inhibition analyses demonstrate significant quantitative immunochemical differences between CEA-S and preparations of carcinoembryonic antigen. These results are consistent with the concept that CEA-S is an immunochemical isomer of carcinoembryonic antigen.


Studies on the uptake of 2-deoxy-d-glucose in normal and malignant rat epithelial liver cells in culture. The rate of uptake of 2-deoxyglucose in normal rat hepatic cells and chemically induced hepatoma cells in culture was studied. The hepatoma cells possessed a higher permeability to the sugar at all stages of culture. However, a decrease in the uptake of 2-deoxyglucose at confluency was observed in cells which exhibited density-dependent inhibition of growth, whether normal or malignant. The normal cells in mitosis showed an increased permeability to the sugar, whereas no such change was observed in the hepatoma cells. The kinetic studies of 2-deoxyglucose transport in normal and transformed rat liver showed a positive correlation between the increase in Vmax and the transformed state of the cells, whether they were transformed in vitro or in vivo. No changes in the apparent Km were found, indicating that there are no qualitative changes in the transport sites. The results suggest that an increase in the number of sites involved in glucose transport is a characteristic of chemically transformed rat liver epithelial cells.


Specific anti-tumor responses by cultured immune spleen cells. I. In vitro culture method and initial characterization of factors which block immune cell-mediated cytotoxicity in vitro. Spleen cells from BALB/c mice which either bore syngeneic sarcomas or were normal controls were cultured in vitro. The culture supernatants of spleen cells from tumor-bearing mice inhibited (blocked) specific cell-mediated cytotoxicity to the tumor borne by the spleen donor. They also mediated specific antiserum-dependent cytotoxicity with control lymphoid cells. The appearance of blocking activity in culture supernatants was prevented by lysis of theta-positive spleen cells with antiserum and complement. The blocking activity was removed by passing culture supernatants through an anti-mouse immunoglobulin affinity column and was recovered in a 3 M NaSCN eluate of the column.


Inhibition of human leukocyte migration in agarose by kcl extracts of carcinoma of the lung. The leukocyte migration in agarose assay recently developed by Clausen (Clausen, 1971), was used to test 22 lung cancer patients against soluble extracts of allogeneic lung cancer and allogeneic normal lung. Seventeen were inhibited to a significantly greater degree by at least one tumor extract (average migration index (MI equals 0.58) than by the corresponding normal lung extract (average MI equals 0.83). DNCB-positive and DNCB-negative patients reacted with equal frequency to tumor extracts. Three patients tested against their autologous tumor and normal lung extracts were specifically inhibited by the tumor extract (average MI equals 0.53) but not by the normal lung extract (average MI equals 0.83). None of seven lung cancer patients tested against non-pulmonary tumor extracts was significantly inhibited (average MI equals 1.1). Only 6/53 controls including patients with other tumors, patients with emphysema and age-matched non-smokers showed significant inhibition against any of the lung cancer extracts. These findings strongly suggest the presence of tumor-associated antigens in KCl-solubilized extracts of human lung cancer.


Induction of malignant lymphomas in swiss mice by n-nitroso compounds formed in vivo. Malignant lymphomas were induced in Swiss mice treated intragastrically with methyl-2-benzimidazole carbamate (MBC, BCM, Carbendazim) and given sodium nitrite in their drinking water. The tumours appeared between 82 and 164 days after the beginning of treatment. In 30 mice given MBC and sodium nitrite, 10 lymphosarcomas were found. In the proliferating tumour cells, intracytoplasmic type-A virus particles were demonstrated by electron microscopy. No tumours were found in animals given MBC only. The findings demonstrate the possibility of in vivo formation of N-nitroso derivatives from MBC.


Murine sarcoma virus related nucleic acid sequences in a non-transforming virus derived from an interspecies pseudotype sarcoma virus. A number of sarcomagenic viruses recovered from hamster tumors induced originally by Moloney sarcoma virus or several of its mouse pseudotypes appear to be interspecies pseudotypes with structural proteins of hamster type-C viruses and nucleic acid sequences of both mouse and hamster specificity. A non-transforming virus (GLOH-minus) recovered from a sarcomagenic virus preparation obtained from a tumor induced by the Gross pseudotype of Moloney sarcoma virus was previously shown to retain mouse sequences. The ability to discriminate readily between Gross and Moloney viruses by molecular hybridization, especially with regard to thermal stability of inter-strain hybrid molecules, and the stability of Moloney virus sequences in a rat-mouse interspecies pseudotype, made it possible to specify that the mouse virus-specific sequences in GLOH-minus are derived from Moloney virus and not Gross. Thus, even though GLOH-minus is non-transforming in vitro or in vivo, it still retains sequences highly related to Moloney sarcoma virus. The lack of transforming ability is thus probably based on loss or change of specific sequences necessary for transformation at some point in the history of this virus.


[Analog computer analysis of radioactivity kinetics in man following oral administration of tilidine HCl-14C]. Models for studying the absorption and elimination kinetics of 14-C labelled DL-Ethyl-trans-2-dimethylamino-1-phenyl-cyclohex-3-ene-trans-1-carboxylate-hydrochloride (Tilidine - HCl, Valoron) are developed, based on the concentration vs. time of radioactivity in the plasma following a single oral administration in man. For this purpose, the average concentration values in the plasma of 3 healthy adults, as given by Vollmer and Poisson [12] were employed. 1. Two three-compartment-models were developed which simulate with sufficient accuracy the 14-C-Valoron concentration curve in the plasma. 2. Computer analysis enables one to determine the distribution of 14-C-Valoron among the intra- and extravasal compartments and the half life for absorption t1/2 equals 0.57 h, for transport from plasma into the extravasal compartment t1/2 equals 3.31 h, for resorption t1/2 equals 4.11 h, for elimination with feces t1/2 equals 29.5 h and for elimination in urine t1/2 equals 8.75 h. 3. The use of two different models allows one to draw conclusions concerning the participation of parenchymatous organs in storage and elimination. 4. The probable radioactivity curve is calculated for repeated oral application of 14-C-Valoron in 8 hours intervals.


Ultrasonic extraction of total particulate aromatic hydrocarbons (TpAH) from airborne particles at room temperature. A superior enrichment procedure for the extraction of TpAH from airborne particles collected on glass fiber filter paper is described. The sample is suspended in a solvent and subjected to ultrasonic waves at room temperature with glass powder to adsorb polar coextractives. The TpAH in the filtered extracts are separated from other compounds by high speed liquid chromatography. Sensitivity is in the nanogram range, and the procedure is highly reproducible. Significantly larger amounts of TpAH are recovered than with Soxhlet extraction for 6 to 8 hours, and the percentage of pAH in the extracts is much higher. The entire procedure requires approximately 40 minutes, most of which is waiting time.